An agonist is a chemical that binds to the receptor of a cell and activates the receptor to cause a physiological response. An agonist initiates the same reaction typically produced by the binding of an endogenous ligand (such as a hormone or neurotransmitter) with a receptor. A drug’s ability to affect a given receptor is dependent on the drug’s affinity and intrinsic efficacy towards that receptor. The affinity of a drug describes the strength of attraction between it and a given receptor, and consequently its ability to bind to that receptor. A drug with a high affinity for a receptor has a high likelihood of binding to it, while a drug with a low affinity has a lesser degree of attraction towards a receptor.
This contrasts the efficacy of a drug, which describes a drug's capacity to produce a response when bound to a receptor. A drug with high efficacy will produce a proportionally stronger effect than a drug of lower efficacy occupying the same number of receptors. The maximum efficacy of a drug reflects the greatest attainable response to a particular drug on a receptor set regardless of dose. A drug with a high efficacy may need to occupy less receptors to produce maximum effects, meaning it will not produce stronger effects beyond a certain dosage.
In contrast to an agonist, an antagonist is a chemical that binds to the receptor of a cell without causing a physiological response. Receptor antagonists work by blocking or diminishing the effects produced by endogenous or drug-induced agonism of a receptor.
Types of agonists
Receptors can be activated by chemicals produced by the body (endogenous) or chemicals from outside of the body (exogenous). Therefore, an endogenous agonist for a particular receptor is a chemical produced in the body that binds to and activates that receptor. For example, serotonin is the endogenous agonist of serotonin receptors.
There are several types of agonist:
- A superagonist is an agonist that produces a greater effect from the receptor than the endogenous agonist, and therefore has an efficacy of over 100%.
- A full agonist binds and activates a receptor with an efficacy equal to the endogenous agonist. For example, heroin mimics the action of endorphins on μ-opioid receptors in the nervous system.
- A partial agonist binds and activates a receptor with less efficacy than the endogenous agonist. For example, psilocin is a partial agonist of the 5-HT2A receptor.
An inverse agonist is an agent that binds to the same receptor as an agonist, but triggers the opposite pharmacological effect of a receptor agonist. Inverse agonists can only act on receptors with constitutive activity; these receptors produce a biological response without the presence of an agonist. An agonist increases a receptor activity above its baseline, while an inverse agonist decreases the receptor activity below its baseline. For example, naloxone is a partial inverse agonist to μ-opioid receptors.
An allosteric modulator is a substance which indirectly influences (modulates) the effects of an agonist or inverse agonist at a target protein (for example, a receptor). Allosteric modulators bind to a site distinct from that of the agonist binding site. Usually they induce a change within the protein structure. A positive allosteric modulator induces an amplification, while a negative modulator induces an attenuation of the effects of the ligand without triggering a functional activity on its own in the absence of the ligand.
- Agonist definition (Merriam-Webster) http://www.merriam-webster.com/dictionary/agonist